Carbon Monoxide Alleviates Cardiomyocyte Pyroptosis in Diabetic Cardiomyopathy by Downregulating the IL-33/ST2L Axis.

OBJECTIVES: This study aimed to investigate whether carbon monoxide (CO) can alleviate cardiomyocyte pyroptosis by downregulating the IL-33/ST2L axis in diabetic cardiomyopathy (DCM). METHODS: The diabetic mouse model was established and treated with CO-releasing molecule-2 (CORM-2) or invalid CORM-2 (iCORM-2). For in vitro studies, cardiomyocytes were treated with high glucose (HG). RESULTS: The HG-treated cardiomyocytes exhibited increased IL-33, ST2L, and pyroptosis-related protein expression compared with that in the control group (p < 0.05). Treatment with recombinant IL-33 further increased the expression of HG-induced pyroptosis-related proteins (p < 0.05). Compared with control mice, DCM mice showed reduced cardiac function and elevated expression of IL-33, ST2L, and pyroptosis-related proteins (p < 0.01). Intervention with CORM-2 ameliorated cardiac injury, and decreased the expression of IL-33, ST2L, and pyroptosis-related proteins in vivo and in vitro (p < 0.05). However, iCORM-2 had no effect both in vivo and in vitro. CONCLUSIONS: In conclusion, CO may inhibit cardiomyocyte pyroptosis by downregulating the IL-33/ST2L axis in DCM mice.